Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus to which up to 80% of normal people will have been exposed by the time they reach adulthood. In many cases the virus produces an asymptomatic infection but, in other cases, a full blown mononucleosis-type syndrome may develop. During active infection, the virus sequentially expresses its immediate-early (IE), early and late genes. As is typical for the herpesvirus family, HCMV can also exist in a latent state, during which time only the IE genes are expressed. The IE region consists primarily of two genes (IE1 and IE2). IE1 and IE2 code for proteins which act in trans to regulate their own production as well as the expression of the early and late genes. These proteins are primarily expressed in the nucleus of cells, but are also expressed, to a lesser degree, on the cell surface where they can act as potent antigens to trigger an immune response. HCMV can also reactivate from the latent state under conditions of immunosuppression, resulting in clinically apparent disease. The effect on the lung of this virus or other viruses in their latent state is unknown. However, in the latent state, these viral IE proteins could cause a chronic antigenic stimulus in the lung as well as modulate expression of various cytokine genes which are important to the inflammatory response in the lung. Interstitial lung diseases are characterized by ongoing, chronic inflammation resulting in fibrosis and scarring of the lung parenchyma. Although most of these diseases are idiopathic in nature, some of the patients date their onset of symptoms to a prodromal viral illness. Studies that have already been performed which attempted to culture virus from the lung do not exclude a role for these viruses since latent viruses (which are not replicating at the time of culture) would not be isolated by these techniques. The unique capacity, however, of latent viral gene products to act as both a chronic antigenic stimulus and to alter the regulation of cell genes that are important in the inflammatory response in the lung suggest that further studies of latent viral infections are warranted in relation to the pathogenesis of chronic interstitial lung diseases. To date, however, with the exception of bronchiolitis obliterans (see Pathology Core), there is no direct evidence that viruses play a role in the pathogenesis of other interstitial lung diseases. A consistent feature of many of the interstitial lung diseases, while they are active, is a persistent expression of cytokine genes that are important to maintain an inflammatory response in the lung. For example, both bleomycin and silica have been used as models for the study of idiopathic interstitial lung disease. In both models there are studies which demonstrate the necessity for the expression of tumor necrosis factor (TNF)